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  • Cytosine/*analogs & derivatives/metabolism  (1)
  • Decision models  (1)
  • Embryonic Stem Cells  (1)
  • Induced Pluripotent Stem Cells/metabolism  (1)
  • Proto-Oncogene Proteins/genetics/*metabolism  (1)
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  • 1
    Publication Date: 2011-08-06
    Description: The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462231/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462231/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Yu-Fei -- Li, Bin-Zhong -- Li, Zheng -- Liu, Peng -- Wang, Yang -- Tang, Qingyu -- Ding, Jianping -- Jia, Yingying -- Chen, Zhangcheng -- Li, Lin -- Sun, Yan -- Li, Xiuxue -- Dai, Qing -- Song, Chun-Xiao -- Zhang, Kangling -- He, Chuan -- Xu, Guo-Liang -- 1S10RR027643-01/RR/NCRR NIH HHS/ -- GM071440/GM/NIGMS NIH HHS/ -- R01 GM071440/GM/NIGMS NIH HHS/ -- S10 RR027643/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 2;333(6047):1303-7. doi: 10.1126/science.1210944. Epub 2011 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Group of DNA Metabolism, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817016" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; DNA/*metabolism ; DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic Stem Cells ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Oxidation-Reduction ; Proto-Oncogene Proteins/genetics/*metabolism ; RNA, Small Interfering ; Thymine DNA Glycosylase/genetics/*metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 55 (1994), S. 243-248 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Bone density ; Longitudinal studies ; Statistical models ; Decision models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract We calculated how long to wait before repeating bone mineral density (BMD) measurements to reassess fracture risk. Correlation results from serial measurements of 495 postmenopausal Japanese-American women were used to estimate 95% confidence intervals (CI) for future BMD. After 7 years of follow-up, BMD correlations with the initial measurement ranged between 0.81 and 0.94, depending on age group and measurement site. In this analysis, the period between measurements was defined as the time required for the lower 95% CI to fall below the BMD value corresponding to doubling of fracture risk. Progressive bone loss causes fracture risk to double after 10 years, on average. However, the 95% CIs indicate that a second BMD measurement will detect risk doubling after only 2 or 3 years for some women. For untreated, early postmenopausal women, the period between measurements was approximately 2–5 years for the radius and 4–6 years for the calcaneus, depending on the initial BMD level. The period was approximately 1 year longer for women age 60 and older. Treatments that halve the bone loss rate would increase the period by 1–3 years. In the absence of a second measurement of BMD, the CI will continue to expand with time, corresponding to a wider range in risk between individuals, and a greater proportion of women will be at increased fracture risk. Obtaining a second BMD measurement pinpoints the patient's status within the precision of the measurement. We conclude that repeated BMD measurements will provide a more accurate estimate of fracture risk than a single, baseline measurement.
    Type of Medium: Electronic Resource
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